darunavir ethanolate

darunavir ethanolate

Prezista

Pharmacologic class: Protease inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category B

Action

Inhibits human immunodeficiency virus-1 (HIV-1) protease, preventing formation of mature virus particles

Availability

Tablets: 300 mg

⊘Indications and dosages

➣ HIV infection in adults who've previously received antiretrovirals

Adults: 600 mg (two 300-mg tablets) P.O. twice daily, taken with ritonavir or other antiretrovirals

Contraindications

• Hypersensitivity to drug or its components (including sulfa)
• Concurrent administration with drugs highly dependent on CYP3A for clearance and for which elevated levels are linked to serious or life-threatening events (including astemizole, cisapride, dihydroergotamine, ergonovine, ergotamine, methylergonovine, midazolam, pimozide, terfenadine, and triazolam)

Precautions

Use cautiously in:
• diabetes mellitus, hemophilia, hepatic dysfunction or disease
• concurrent use of carbamazepine, lovastatin, phenobarbital, phenytoin, rifampin, simvastatin, or St. John's wort (use not recommended)
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Give twice daily with ritonavir and food.
☞ Don't give concurrently with astemizole, cisapride, dihydroergotamine, ergonovine, ergotamine, methylergonovine, midazolam, pimozide, terfenadine, or triazolam.

Route	Onset	Peak	Duration
P.O.	Unknown	2.5-4 hr	Unknown

Adverse reactions

CNS: asthenia, fatigue, headache, transient ischemic attack, confusion, disorientation, anxiety, irritability, altered mood, memory impairment, vertigo, rigors, peripheral neuropathy, paresthesia, hypoesthesia, somnolence, nightmares

CV: tachycardia, hypertension, myocardial infarction

EENT: nasopharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, abdominal distention, flatulence, dry mouth, anorexia

GU: renal insufficiency, nephrolithiasis, polyuria, gynecomastia, acute renal failure

Metabolic: diabetes mellitus, polydipsia, obesity

Musculoskeletal: arthralgia, myalgia, extremity pain, osteopenia, osteoporosis

Respiratory: dyspnea, cough

Skin: allergic dermatitis, eczema, inflammation, toxic skin eruption, dermatitis medicamentosa, hyperhidrosis, folliculitis, maculopapular rash, alopecia, erythema multiforme, Stevens-Johnson syndrome

Other: body fat redistribution, lipoatrophy, decreased appetite, hiccups, pyrexia, night sweats, hyperthermia, peripheral edema, immune reconstitution syndrome (inflammatory response to indolent or residual opportunistic infections)

Interactions

Drug-drug. Amiodarone, atorvastatin, bepridil, clarithromycin, cyclosporine, felodipine, fluticasone propionate (inhalation), lidocaine (systemic), nicardipine, nifedipine, pravastatin, quinidine, sildenafil, sirolimus, tacrolimus, tadalafil, trazodone, vardenafil: increased blood levels of these drugs

Astemizole, cisapride, terfenadine: increased risk of serious or life-threatening reactions (such as arrhythmias)

Carbamazepine, dexamethasone (systemic), phenobarbital, phenytoin, rifampin: decreased darunavir blood level

Efavirenz: decreased blood levels of both drugs

Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine): increased risk of acute ergot toxicity

Hormonal contraceptives: decreased ethinyl estradiol blood level; may decrease contraceptive efficacy

Itraconazole, ketoconazole: increased blood levels of these drugs and darunavir

Lopinavir/ritonavir, saquinavir: decreased effects of these drugs

Lovastatin, pimozide, simvastatin: increased risk of myopathy

Methadone, voriconazole, warfarin: decreased blood levels of these drugs

Midazolam, triazolam: increased risk of respiratory depression or increased sedation

Paroxetine, sertraline: decreased effects of these drugs

Rifabutin: increased rifabutin blood level, decreased darunavir blood level (when given with ritonavir)

Voriconazole: decreased voriconazole and increased darunavir blood levels

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, gamma-glutamyltransferase, lipase, lipids, partial thromboplastin time, plasma prothrombin time, total cholesterol, triglycerides, uric acid: increased levels

Bicarbonate, calcium, lymphocytes, platelets, total absolute neutrophils, white blood cells: decreased levels

Bilirubin, serum glucose, sodium: increased or decreased levels

Drug-food. Any food: increased drug absorption

Drug-herbs. St. John's wort: decreased darunavir blood level

Patient monitoring

• During initial treatment phase, stay alert for immune reconstitution syndrome.
• Monitor liver function studies frequently in patients with preexisting hepatic dysfunction or disease.
• Monitor blood glucose levels frequently in patients with diabetes mellitus.
• Carefully monitor patient receiving antiarrhythmics and HMG-CoA reductase inhibitors while taking this drug.
• Monitor International Normalized Ratio when giving drug with warfarin.

Patient teaching

• Instruct patient to take drug with ritonavir and food, as prescribed.
• Advise patient to inform prescriber of other drugs and supplements he's taking (including vitamins and herbs) before starting drug or taking new medication.
☞ Urge patient to immediately report side effects (especially rash).
• Emphasize that drug doesn't cure HIV infection.
• Advise patient using hormonal contraceptives to use alternative contraceptive method while taking this drug.
• Advise patients who are pregnant or recently gave birth not to breastfeed because of risk of passing HIV infection to infant and potentially serious adverse drug reactions.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.